RDEA3170 and Febuxostat Combination Study in Gout Subjects

A Phase 2a, Randomized, Open-Label Study to Evaluate the Pharmacodynamic Effects and Safety of RDEA3170 Administered in Combination With Febuxostat Compared to Febuxostat Administered Alone in Adult Subjects With Gout

This is a Phase 2a, randomized, open-label, multicenter study to assess the pharmacodynamic (PD) effects and safety of RDEA3170 administered in combination with febuxostat compared to febuxostat administered alone in adult subjects with gout.

Study Overview

• Status: Completed
• Conditions: Gout
• Intervention / Treatment: Drug: RDEA3170 10 mg; Drug: Febuxostat 40 mg; Drug: Febuxostat 80 mg; Drug: RDEA3170 15 mg; Drug: RDEA3170 5 mg; Drug: RDEA3170 2.5

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
    • Glendale, California, United States, 91206
  • Florida
    • South Miami, Florida, United States, 33143
  • Kansas
    • Overland Park, Kansas, United States, 66211
    • Overland Park, Kansas, United States, 66212
  • Texas
    • Dallas, Texas, United States, 75231

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Able to understand the study procedures and the risks involved and is willing to provide written informed consent before the first study-related activity.
• Meets one or more criteria for the diagnosis of gout as per the American Rheumatism Association Criteria for the Classification of Acute Arthritis of Primary Gout.
• Body weight ≥ 50 kg (110 lbs) and a body mass index ≥ 18 and ≤ 45 kg/m2.
• Screening serum urate level ≥ 8 mg/dL.
• Free of any clinically significant disease or medical condition, per the Investigator's judgment.

Exclusion Criteria:

• Unable to take colchicine for gout flare prophylaxis.
• History or suspicion of kidney stones.
• Any gastrointestinal disorder that affects motility and/or absorption.
• Unstable angina, New York Heart Association class III or IV heart failure, ischemic heart disease, stroke, or deep venous thrombosis within 12 months prior to Day 1; or subject is currently receiving anticoagulants.
• Screening laboratory parameters that are outside the normal limits and are considered clinically significant by the Investigator.
• Estimated creatinine clearance < 60 mL/min calculated by the Cockcroft-Gault formula using ideal body weight during the Screening period.
• Taking losartan, fenofibrate, guaifenesin, or sodium-glucose linked transporter-2 inhibitors; chronic and stable doses are permitted if doses are stable for at least 14 days prior to study medication dosing.
• Unable or unwilling to comply with the study requirements or has a situation or condition that, in the opinion of the Investigator, may interfere with participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: RDEA3170 10 mg; Once daily (qd) with febuxostat 40mg (qd) for 7 days, and with febuxostat 80 mg (qd) for 7 days; febuxostat 40 mg (qd) only for 7 days, and febuxostat 80 mg (qd) only for 7 days.	Drug: RDEA3170 10 mg; Drug: Febuxostat 40 mg; Drug: Febuxostat 80 mg
EXPERIMENTAL: RDEA3170 15 mg; Once daily with febuxostat 40mg (qd) for 7 days and with febuxostat 80mg (qd) for 7 days; febuxostat 40 mg (qd) only for 7 days, and febuxostat 80 mg (qd) only for 7 days.	Drug: Febuxostat 40 mg; Drug: Febuxostat 80 mg; Drug: RDEA3170 15 mg; Drug: RDEA3170 5 mg
EXPERIMENTAL: RDEA3170 5 mg; Once daily with febuxostat 40mg (qd) for 7 days and with febuxostat 80mg (qd) for 7 days; febuxostat 40 mg (qd) only for 7 days, and febuxostat 80 mg (qd) only for 7 days.	Drug: Febuxostat 40 mg; Drug: Febuxostat 80 mg
EXPERIMENTAL: RDEA3170 2.5 mg; Once daily with febuxostat 40mg (qd) for 7 days and with febuxostat 80mg (qd) for 7 days; febuxostat 40 mg (qd) only for 7 days, and febuxostat 80 mg (qd) only for 7 days.	Drug: Febuxostat 40 mg; Drug: Febuxostat 80 mg; Drug: RDEA3170 2.5

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Urate Maximum Percentage (%) Change (Emax, CB)	Maximum observed percentage (%) change from baseline in serum urate concentrations.	28 days
Urine Uric Acid % Change (0-24h) (Aeur, CB)	Percentage (%) change from baseline in the amount of uric acid recovered in urine.	28 days
Renal Clearance of Uric Acid % Change (0-24h) (CLur, CB)	Percentage (%) change from baseline in renal clearance of uric acid.	28 days
Fract. Excretion of Uric Acid % Change (0-24h) (FEUA, CB)	Percentage (%) change from baseline in fractional excretion of uric acid.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax)	Cmax of multiple-dose RDEA3170 administered in combination with febuxostat from plasma	Days 7 to 28
Time of Occurrence of Maximum Observed Concentration (Tmax)	Tmax of multiple-dose RDEA3170 administered in combination with febuxostat from plasma	Days 7 to 28
Area Under the Concentration-time Curve From Time Zero up to 24 Hours Postdose (AUC 0-24)	AUC 0-24 of multiple-dose RDEA3170 administered in combination with febuxostat from plasma	Days 7 to 28
Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last)	AUC last of multiple-dose RDEA3170 administered in combination with febuxostat from plasma	Days 7 to 28
Apparent Terminal Half-life (t1/2)	t1/2 of multiple-dose RDEA3170 administered in combination with febuxostat from plasma	Days 7 to 28
Incidence of Treatment-Emergent Adverse Events		10 weeks

Collaborators and Investigators

• Sponsor: Ardea Biosciences, Inc.

Publications and helpful links

General Publications

• Rekic D, Johansson S, Leander J. Higher Febuxostat Exposure Observed in Asian Compared with Caucasian Subjects Independent of Bodyweight. Clin Pharmacokinet. 2021 Mar;60(3):319-328. doi: 10.1007/s40262-020-00943-6. Epub 2020 Sep 19.
• Fleischmann R, Winkle P, Hall J, Valdez S, Liu S, Yan X, Hicks L, Lee C, Miner JN, Gillen M, Hernandez-Illas M. Pharmacodynamic and pharmacokinetic effects and safety of verinurad in combination with febuxostat in adults with gout: a phase IIa, open-label study. RMD Open. 2018 Apr 9;4(1):e000647. doi: 10.1136/rmdopen-2018-000647. eCollection 2018.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (ACTUAL): July 1, 2015
• Study Completion (ACTUAL): February 1, 2016

Study Registration Dates

• First Submitted: September 19, 2014
• First Submitted That Met QC Criteria: September 19, 2014
• First Posted (ESTIMATE): September 23, 2014

Study Record Updates

• Last Update Posted (ACTUAL): July 27, 2017
• Last Update Submitted That Met QC Criteria: June 27, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Metabolism, Inborn Errors; Crystal Arthropathies; Purine-Pyrimidine Metabolism, Inborn Errors; Gout; Antirheumatic Agents; Gout Suppressants; Febuxostat; Verinurad
• Other Study ID Numbers: RDEA3170-204